Lithium potassium titanium oxide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Sept-Oct 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study has been performed according to OECD and EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

(1981)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Lithium Potassium Titanium Oxide

EC Number:

445-620-6

Cas Number:

39318-30-4

Molecular formula:

Hill Empirical formula: K(0.5-0.7) Li(0.27) Ti(1.73) O(3.8-3.95) CAS Empirical formula: K(0.5-0.7) Li(0.27) Ti(1.73) O(3.8-3.95)

IUPAC Name:

Lithium Potassium Titanium Oxide

Details on test material:

Name of test substance cited in the test report: Terracess L
Batch no. : IH80
Expiry date: August 2002
Specific gravity: 3.3 g/cm3
Physical form of substance: white non-hygroscopic powder

Test animals

Species:

rat

Strain:

other: Wistar, SPF-reared, Wistar derived (Crl:[WI]WU BR)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS (5 males/5 females)
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: 5-6 weeks (before acclimatisation)
- Weight at study initiation: the mean body weights of the rats were 271 g and 184 g for male and female animals, resp., just before exposure.
- Earmark for identification
- Housing: Conventional conditions in suspended stainless steel cages fitted with wire-mesh floor and front
- Diet: a commercially available rodent diet (Rat & Mouse No. 3 Breeding Diet RM3) from SDS Special Diets Services, Witham, England).
- Water: Tap water suitable for human consumption.
- Acclimation period: 26 days
- No access to feed or water during exposure.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): between 20.5 and 22.5°C
- Humidity (%): between 50 and 86% (values > 70% were limited to not more than 2% of the time)
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: none

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

Exposure in a nose-only inhalation chamber, a modification of the chamber manufactured by ADG developments Ltd., Codicote, Hitchin, Herts. SG4 8 UB, United Kingdom. The inhalation chamber consisted of a cylindrical aluminium column, surrounded by a transparent cylinder. The column had a volume of ca. 50L and consisted of a top assembly with two mixing chambers, underneath a rodent tube section and the exhaust section at the bottom. The rodent tube section had 20 ports for animal exposure. Empty ports were closed if not used for test atmosphere sampling, particle size analysis, measurement of oxygen concentration, temperature and relative humidity.

The animals were secured in plastic animal holders (Batelle), positioned radially through the outer cylinder around the central column. Male and female rats of each group were placed in alternating order. Only the nose of the rat protruded into the interior of the column. By securing a positive pressure in the central column and a slightly negative pressure in the outer cylinder, which encloses the entire animal holder, air leaks from nose to thorax rather than from thorax to nose and dilution of test atmosphere at the nose of the animals is prevented.

The inhalation equipment was designed to expose rats to a continuous supply of fresh test atmosphere. The test atmosphere was generated by passing test material to an eductor (Fox mini, type 060, Spraybest Europe BV, Zwanenburg, the Netherlands) using a dry material feeder (Gericke GMD 60, Gericke AG, Regensburg, Switzerland). The eductor was placed at the inlet of the exposure unit and was operated with pressurized dry air controlled by a pressure reducing valve at 0.5 bar. The test material was delivered in a slip stream of humidified air. The resulting aerosol was directed downwards towards the animal noses. At the bottom of the unit the test atmosphere was exhausted. The mean flow of air was 70 L/min. The period between the start of the generation of the test atmosphere and the start of exposure of animals was 45 minutes.

TEST ATMOSPHERE

The concentration of the aerosol in the test atmosphere was determined once per hour by gravimetric analysis. During exposure, representative samples were obtained by passing 5 L test atmosphere samples at 5 L/min through glass fibre filters (Sartorius, 13430-44-5). Filters were weighed before sampling, loaded with aerosol particles and weighed again.

Particle size distribution measurements were carried out twice in the preliminary phase and twice during exposure using a 1 L-stage cascade impactor (Institute's design) with the largest cut-off size of 4.2 µm. Measured values of the mass median particle size of the particles in the test atmosphere (MMAD) were 2.9 and 3.0 µm and the distribution of particle sizes had a GSD (Geometric st. dev.) of 1.4 µm.

Temperature (22.0 +/- 0.3°C) and humidity (44 +/-1%) in air chamber were recorded eight times during exposure at regular intervals (ca. twice per hour) using an RH/T device (TESTO 610, TESTO GmbH & Co, Lenzkirch, Schwarzwald, Germany) . The oxygen concentration was checked once during exposure (Beryl, Cosma, Igny, France): 21.2%.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

by gravimetric analysis

Duration of exposure:

4 h

Concentrations:

The measured aerosol concentrations during exposure were: 5.018, 5.456, 5.434 and 5.306 g/m3
Mean: 5.3 +/- 0.2 g/m3 (n=4)

The nominal concentration was calculated by dividing the total amount of test material used (by weighing the feeder before the start of the generation and after cessation of the generation) by the total volume of air passed through the exposure unit: 7.7 g/m3.

The generation efficiency was 69% (a common value)

No. of animals per sex per dose:

one group of 5 male and 5 female rats

Control animals:

no

Details on study design:

- Duration of observation period following exposure: 14 days
- Visual inspection of the rats (for behaviour, clinical signs and mortality) just before exposure, shortly after exposure and at least once daily during the observation period.
- Body weights were recorded just before exposure (day 0), on day 7 and on day 14
- Necropsy of survivors performed: yes (at the end of the 14-day observation period)
- All rats were examined for gross pathological changes

Results and discussion

Preliminary study:

None

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.3 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Males: 0/5
Female: 0/5

Clinical signs:

other: Slight irregular breathing in all exposed animals was seen during exposure. A slightly decreased breathing rate and slight laboured breathing were observed athe last two observation periods during exposure. Shortly after exposure soiled fur was seen in o

Body weight:

Overall body weight gain was considered to be within the normal limits for animals of this strain and age.

Gross pathology:

Exposure related abnormalities were not found at necropsy.

Other findings:

During the 14-day observation period, treatment related abnormalities were not observed.

Any other information on results incl. tables

Aerodynamic particle size distribution in the test atmosphere during exposure: MMAD = 2.9 µm (first measurement)/ 3.0 µm (second measurement). Mean geometric standard deviation was 1.4 in both measurements. During preliminary testing MMAD values of 2.7 and 2.9 µm were measured (GSD=1.4).

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Remarks:

according to EU 1272/2008

Conclusions:

The acute inhalation LC50 of Terracess L in rat is > 5.3 mg/L air.
Terracess L does not have to be classified and has no obligatory labelling requirement for inhalation toxicity.